Effect of interleukin-1β on ghrelin receptor in periodontal cells

• DOI: 10.1007/s00784-018-2417-y
• Publication Date: 2018-03-14T15:52:14Z
• Authors: Marjan Nokhbehsaim; Svenja Memmert; Anna Damanaki; Shanika Nanayakkara; Xiaoyan Zhou; Andreas Jäger; James Deschner
• Keywords: Male; Periodontal Ligament; Interleukin-1beta; Gingiva; Fluorescent Antibody Technique; Fibroblasts; Real-Time Polymerase Chain Reaction; Immunohistochemistry; Up-Regulation; 03 medical and health sciences; 0302 clinical medicine; Gene Expression Regulation; Humans; Female; Mitogen-Activated Protein Kinases; Extracellular Signal-Regulated MAP Kinases; Receptors, Ghrelin; Cells, Cultured; Signal Transduction

Periodontopathogens induce immunoinflammatory responses characterized by the release of inflammatory mediators, e.g., interleukin (IL)-1β, IL-6, and IL-8. Ghrelin (GHRL) is an appetite hormone which mediates its effect via the functional receptor GHS-R1a. This study was to examine the effect of an inflammatory insult on GHS-R1a in human periodontal cells.Periodontal ligament (PDL) cells and gingival fibroblasts (HGFs) were exposed to IL-1β in the presence and absence of GHRL. Cells were also pre-incubated with specific inhibitors of NF-κB or MEK1/MEK2 signaling. Gene expression of GHS-R1a and proinflammatory mediators was assessed by real-time PCR, GHS-R1 protein level by immunocytochemistry, and NF-κB nuclear translocation by immunofluorescence.IL-1β increased significantly the GHS-R1a expression in both cell types in a dose-dependent manner. The stimulatory effect of IL-1β involved the NF-κB and MAPK pathways. Exposure of cells to IL-1β also resulted in an increased production of GHS-R1 protein in both cell types. Furthermore, GHRL counteracted significantly the stimulatory actions of IL-1β on IL-6 and IL-8 in PDL cells.This study demonstrates for the first time that IL-1β upregulates the functional ghrelin receptor in periodontal fibroblastic cells. Moreover, these results further support the assumption that the GHRL/GHS-R system exerts anti-inflammatory effects. Therefore, the upregulation of ghrelin receptor in periodontal cells in response to an inflammatory stimulus may represent a negative feedback mechanism to attenuate the initial inflammatory process in periodontal diseases.The anti-inflammatory GHRL/GHS-R system may serve as a promising target for the prevention and therapy of periodontal diseases.